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Matsuo, Toshihiko Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University ORCID Kaken ID publons researchmap
Hamasaki, Ichiro Department of Ophthalmology, Okayama University Hospital Kaken ID
Kamatani, Yoichiro Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo
Kawaguchi, Takahisa Center for Genomic Medicine, Graduate School of Medicine, Kyoto University
Yamaguchi, Izumi Center for Genomic Medicine, Graduate School of Medicine, Kyoto University
Matsuda, Fumihiko Center for Genomic Medicine, Graduate School of Medicine, Kyoto University
Saito, Akira StaGen Co., Ltd.
Nakazono, Kazuyuki StaGen Co., Ltd.
Kamitsuji, Shigeo StaGen Co., Ltd.
Abstract
Esotropia and exotropia in the entity of comitant strabismus are multifactorial diseases with both genetic and environmental backgrounds. Idiopathic superior oblique muscle palsy, as the predominant entity of non-comitant (paralytic) strabismus, also has a genetic background, as evidenced by varying degrees of muscle hypoplasia. A genome-wide association study (GWAS) was conducted of 711 Japanese patients with esotropia (n= 253), exotropia (n = 356), and idiopathic superior oblique muscle palsy (n = 102). The genotypes of single nucleotide polymorphisms (SNPs) were determined by Infinium Asian Screening Array. Three control cohorts from the Japanese population were used: two cohorts from BioBank Japan (BBJ) and the Nagahama Cohort. BBJ (180K) was genotyped by a different array, Illumina Infinium OmniExpressExome or HumanOmniExpress, while BBJ (ASA) and the Nagahama Cohort were genotyped by the same Asian array. After quality control of SNPs and individuals, common SNPs between the case cohort and the control cohort were chosen in the condition of genotyping by different arrays, while all SNPs genotyped by the same array were used for SNP imputation. The SNPs imputed with R-square values ≥ 0.3 were used to compare the case cohort of each entity or the combined entity with the control cohort. In comparison with BBJ (180K), the esotropia group and the exotropia group showed CDCA7 and HLA-F, respectively, as candidate genes at a significant level of p < 5 × 10−8, while the idiopathic superior oblique muscle palsy group showed DAB1 as a candidate gene which is involved in neuronal migration. DAB1 was also detected as a candidate in comparison with BBJ (ASA) and the Nagahama Cohort at a weak level of significance of p < 1 × 10−6. In comparison with BBJ (180K), RARB (retinoic acid receptor-β) was detected as a candidate at a significant level of p < 5 × 10−8 in the combined group of esotropia, exotropia, and idiopathic superior oblique muscle palsy. In conclusion, a series of GWASs with three different control cohorts would be an effective method with which to search for candidate genes for multifactorial diseases such as strabismus.
Keywords
esotropia
exotropia
superior oblique muscle palsy
genome-wide association study
comitant strabismus
non-comitant strabismus
Japanese population
BioBank Japan
Nagahama Cohort
Asian array
Published Date
2024-06-26
Publication Title
International Journal of Molecular Sciences
Volume
volume25
Issue
issue13
Publisher
MDPI
Start Page
6986
ISSN
1422-0067
Content Type
Journal Article
language
English
OAI-PMH Set
岡山大学
Copyright Holders
© 2024 by the authors.
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isVersionOf https://doi.org/10.3390/ijms25136986
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https://creativecommons.org/licenses/by/4.0/
Citation
Matsuo, T.; Hamasaki, I.; Kamatani, Y.; Kawaguchi, T.; Yamaguchi, I.; Matsuda, F.; Saito, A.; Nakazono, K.; Kamitsuji, S. Genome-Wide Association Study with Three Control Cohorts of Japanese Patients with Esotropia and Exotropia of Comitant Strabismus and Idiopathic Superior Oblique Muscle Palsy. Int. J. Mol. Sci. 2024, 25, 6986. https://doi.org/10.3390/ijms25136986